Studies performed to investigate the mechanisms of T cell recognition of tumor cells bearing altered histocompatibility antigens have revealed that a variety of soluble factors may be involved in normal host-tumor interactions. We have identified soluble factors produced by tumor-bearing mice which are capable of modifying the MHC phenotype of tumor cells. In addition, we have identified soluble factors secreted by some tumor cells which are capable of stimulating the proliferation of host lymphocytes. These findings suggest that the development of the host immune response may involve a complex interplay between host and tumor cells. At present, this interplay is most obvious in the appearance of soluble factors produced in vivo by host and cells. A precise characterization of such soluble factors and the mechanisms by which they exert their influence on host and tumor cells should provide significant insight into the role of host-tumor interactions in the host immune response and the process of tumorigenesis. We have identified host-derived, soluble factors capable of altering the MHC phenotype of tumor cells, and tumor-derived, soluble factors capable of stimulating proliferation of host lymphocytes. On the basis of the data which we presently have available, these soluble factors appear to be different from any previously defined cytokines. We propose to isolate these molecules using standard biochemical methodology, and to extensively characterize their chemical and physical properties. Furthermore, we will identify the specific targets for each of these soluble factors and determine their mechanism of action. Finally, we will investigate a variety of host-tumor systems and establish the general relevance of our observation and the roles of these soluble factors in the metastatic and tumorigenic aspects of the malignant phenotype. Information gathered from these experiments should help to elucidate the mechanisms involved in the generation of both allogeneic and antitumor immune responses. Knowledge of these aspects of the activation of immunocompetent cells should significantly facilitate efforts toward intervention and modification of the immune response, and, in particular, efforts directed toward immunotherapy of human malignancies. (CS)